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Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.
Chen, Fang; Wang, Xingyan; Jang, Seon-Kyeong; Quach, Bryan C; Weissenkampen, J Dylan; Khunsriraksakul, Chachrit; Yang, Lina; Sauteraud, Renan; Albert, Christine M; Allred, Nicholette D D; Arnett, Donna K; Ashley-Koch, Allison E; Barnes, Kathleen C; Barr, R Graham; Becker, Diane M; Bielak, Lawrence F; Bis, Joshua C; Blangero, John; Boorgula, Meher Preethi; Chasman, Daniel I; Chavan, Sameer; Chen, Yii-Der I; Chuang, Lee-Ming; Correa, Adolfo; Curran, Joanne E; David, Sean P; Fuentes, Lisa de Las; Deka, Ranjan; Duggirala, Ravindranath; Faul, Jessica D; Garrett, Melanie E; Gharib, Sina A; Guo, Xiuqing; Hall, Michael E; Hawley, Nicola L; He, Jiang; Hobbs, Brian D; Hokanson, John E; Hsiung, Chao A; Hwang, Shih-Jen; Hyde, Thomas M; Irvin, Marguerite R; Jaffe, Andrew E; Johnson, Eric O; Kaplan, Robert; Kardia, Sharon L R; Kaufman, Joel D; Kelly, Tanika N; Kleinman, Joel E; Kooperberg, Charles.
Afiliação
  • Chen F; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
  • Wang X; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
  • Jang SK; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
  • Quach BC; RTI International, Research Triangle, NC, USA.
  • Weissenkampen JD; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Khunsriraksakul C; Department of Psychology, Penn State College of Medicine, Hershey, PA, USA.
  • Yang L; Deparment of Bioinformatics and Genomics, Penn State College of Medicine, Hershey, PA, USA.
  • Sauteraud R; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
  • Albert CM; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
  • Allred NDD; Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Arnett DK; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Ashley-Koch AE; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Barnes KC; College of Public Health, University of Kentucky, Lexington, KY, USA.
  • Barr RG; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Becker DM; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Bielak LF; Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC, USA.
  • Bis JC; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
  • Blangero J; Department of Medicine, Columbia University Medical Center, New York, NY, USA.
  • Boorgula MP; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Chasman DI; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Chavan S; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
  • Chen YI; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Chuang LM; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Correa A; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
  • Curran JE; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • David SP; Harvard Medical School, Boston, MA, USA.
  • Fuentes LL; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
  • Deka R; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Duggirala R; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Faul JD; Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.
  • Garrett ME; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Gharib SA; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Guo X; University of Chicago, Chicago, IL, USA.
  • Hall ME; NorthShore University Health System, Evanston, IL, USA.
  • Hawley NL; Department of Medicine, Division of Biostatistics and Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.
  • He J; Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Hobbs BD; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Hokanson JE; South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Hsiung CA; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
  • Hwang SJ; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Hyde TM; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Irvin MR; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
  • Jaffe AE; Computational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.
  • Johnson EO; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Kaplan R; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Kardia SLR; Department of Epidemiology (Chronic Disease), School of Public Health, Yale University, New Haven, CT, USA.
  • Kaufman JD; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
  • Kelly TN; Harvard Medical School, Boston, MA, USA.
  • Kleinman JE; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Kooperberg C; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Nat Genet ; 55(2): 291-300, 2023 02.
Article em En | MEDLINE | ID: mdl-36702996
ABSTRACT
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reposicionamento de Medicamentos / Transcriptoma Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reposicionamento de Medicamentos / Transcriptoma Idioma: En Ano de publicação: 2023 Tipo de documento: Article